Targeted alpha therapy (“TAT”) appears promising for treating tumors and other cancers. Targeted alpha therapy employs alpha-emitting radionuclides in combination with a biological targeting vector (e.g. tumor-targeting antibodies or peptides) to selectively destroy cancer cells. Proposed radionuclides for TAT include actinium-225 (t1/2=9.9 days) and its shorter-lived daughter, bismuth-213 (t1/2=45.6 minutes). FIG. 1 provides a schematic block diagram showing the radioactive decay of actinium-225 to bismuth-213. The actinium-225 may be obtained from a radioactive thorium source.
Actinium-225 and bismuth-213 (and also bismuth-212) have undergone clinical trials for cancer treatment with promising results.
Bismuth-212 and bismuth-213 may be used for TAT for the selective destruction of cancerous micro-metastases if an appropriate ligand and biological targeting vector (e.g. antibody, peptide) are employed to deliver these radionuclides to the cancerous cells and stabilize their location at the cancerous cells. The short penetration depth range of alpha particles in biological tissue would minimize toxic side effects resulting from damage of nearby healthy cells.
The rational design of ligands suitable for the chelation and delivery of bismuth ions to a desired location in vivo is difficult. The aqueous coordination chemistry of bismuth ion has been scarcely explored and therefore it is poorly understood. While a variety of ligands have been synthesized and tested for chelation of bismuth radioisotopes, no ideal ligand has been found. In practice, the complexes of bismuth were unstable in vivo; they decomposed, and the resulting uncomplexed bismuth ions distributed to the kidneys.
Ligands that can be functionalized with a biological targeting vector and reacted with a suitable radionuclide to form a complex that is stable in vivo are desirable for targeted alpha therapy.